27

SLEEP THERAPY IN THE TREATMENT OF DUODENAL ULCERS.

BY MICHAEL DILLON

' E v OwtaS"rlmv " ' vocr~ E~VtTEV av~p . . . . . ' '

• O . t r T O V ~crXvpto~ tca't d~Strv~:ro , " 8E vEwa'r~ yao"rp~ . . orro~-E

T H E S E words, coming from a case book more than 2,000 years old, can, in translation, be found in the charts of any hospital pat ient suffering f rom a duodenal ulcer.

* " In Oinidai a man felt ill whenever he was without food, having abdominal pain and severe borborygmi . . . , but immediately a f te r eating anything he always had relief both from the borborygmi and the pain.'-'

To read Hippocrates is to pu t oneself, f rom the point of view of medicine, into a proper perspective and it is great ly to be regret ted that the works of this supreme master of his ar t are not included in the curr icula of medical schools as a set text, for never has so much under- Standing assisted observation, nor observation promoted so much unde;'.- standing, not only of disease and t rauma but also of man himself; for to Hippocrates it was the pat ient who was of first importance and his disease subsidiary to, and to a great extent dependent on, himself. More- over, humili ty is not one of the more marked virtues of the average medical man, and to read Hippocrates is to become aware of the chasm existent between oneself and one's narrowly specialised and modern, materialistic concept of medicine, and the width and scope of his mind unaided by all the apparatus on which we are so dependent to-day.

Those who have forgot ten Hippocrates state that the peptic ulcer was first described by a Frenchman, Jean Cruveilhier, in the middle of the lg th century, fo r which reason the condition has sometimes been known a~ " Cruveilhier 's disease ". But the term " p e p t i c u l c e r " is used con- veniently to cover duodenal and gastric ulcers wherever situated, alfhough thei r clinical manifestations differ considerably. Yet, much can be said of the one that can also be said of the other and, perhaps what is more important, the same questions apply to both, for our know- ledge of their Eetiology and mechanism is still imperfect ; hence, in dis- cussing the duodenal, one cannot omit a reference to the gastric ulcer.

A ~ { o l o g y .

Thus, Cruveilhier 's comments on peptic ulcer deserve reference even though he fails to mention the duodenum, and indeed, as fa r as our knowledge goes at present, one tends to assume that , when the cause of th~ gastric ulcer has been laid bare, t ha t same cause will be found reSponsible for the duodenal lesion. Perhaps ; but i't may not.

" The h is tory of the cause of the simple ulcer of the s tomach , " wrote Cruveilhier, 2 " is surrounded by profound obscurity or, rather, this disease has all the causes of gastritis. But why is a single place

The translation is purposely free.

28 IRISH JOURNAL OF MEDICAL SCIENCE

in the stomach deeply affected and all the other parts of the organ are in a state of perfect integrity? That indeed appears very difficult to explain." I t still is; despite some advance in our understanding of the pathology of the ulcer that question remains unanswered. What progress, then, has been made?

In 1910 Herschell ~ could write : " The tendency of modern research is to show that a duodenal ulcer is caused by the direct action upon the intestinal wall of trypsin and other proteolytic ferments con- tained in the digestive fluids and set free from disintegrated tissue cells and leucocytes." He goes on to postulate the presence of anti- enzymes and anti-lysins in blood serum which, he maintains, are diminished when an ulcer forms. " Under certain conditions . . . ~these antibodies are absent from the blood serum or present in diminished amounts and in consequence the duodenum becomes vulnerable to the lytic fluids with which it comes in contact ." Then all that is required is a local lesion, a point of stress, or of extravasa- ~ion or of the drag of gastroptosis upon an adhesion: with the weakened resistance, an ulcer forms there and not elsewhere and so Cruvelhier's question is answered. But not to everyone's satisfaction. Certainly the facts lend themselves to the hypothesis that whatever Other contributory causes there may be, there must be some deficiency in the alimentary wall at one point to produce an ulcer there and not elsewhere.

Unfortunately the matter is not so simple as that, for it does not answer the questions: why do no ulcers ever form in the oxyntic cell areas of the stomach wall and why ulcers are so rarely known to occur in the second part of the duodenum? Has Herschell been superseded?

Forty years later FitzGerald and Murphy 4 are writing at length on the results of their researches on the biochemistry of the peptic ulcer and they show that Herschell, though right in principle, was wrong in detail. " Peptic ulcer results from digestion of the lining of the stomach and duodenum by pepsin activated by t tC I . " Pepsin, not trypsin. In forty years we have progressed. " The ulcer develops, therefore, probably due to the ill-adjusted interplay of secretion, neutralisation and a third factor--mucosal resistance." The chief contribution of FitzGerald and Murphy, however, lies in the work they have done on urease, which, evidence suggests, may be this third factor--a factor of the mucosal resistance itself, for it is an enzyme found also in the kidneys, hypophysis and liver, but in smaller concentrations. Of considerable interest is the quantita¢ive distribution of this substance as given by these writers. The amount found in the duodenum, they say, is but a fraction of the gastric con- centration, and in the stomach itself the greatest amount appears to be centred in the upper region of Che fundus proper and next to the pyloric area. Let us refer back to Cruveilhier for a moment : " Almost always single, the ulcer is situated most commonly either on the smaller curvature or upon the posterior wall of the stomach. Some- times it invades the pylorus." Certainly an ulcer in the fundus would b ~ a r a t a a v i s , for there and there alone are the oxyntic or acid- bearing cells, cells which, unless provision were made, would inevit-

SLEEP THERAPY IN DUODENAL ULCER 29

ably erode their own matrix, and there, too, is this urease in highest £oneentration.

But what of the duodenum? A duodenal ulcer is commoner than an ulcer on the lesser curvature of the stomach; statistics would suggest that it is becoming even more frequent; and the urease content here is low, much lower than in the gastric mucosa. But the problem of the second part of the duodenum again offel~ a stumbling- block to our edifice of theorising, for, as we have seen, only very occasionally has an ulcer been known to occur at this site. Urease, apparently, is therefore not the complete answer. FitzGerald and Murphy suggest that gastric ulcers are caused by failure in the pro- duction of ammonia by the urease mechanism due to vascular spasm "~r .local emboli. Hence, either this view is false or the cause of duodenal ulcers differs from that of gastric ulcers as suggested above.

Auxiliary to urease is mucus which, as has been known for some time, opposes the corrosive action of t~C1 and, if damage to the gastric wall occurs, deposits itself in considerable quantity over the site, neutralising the acid and offering a protective covering. In addition, the third defence mechanism is the presence of ammonia in the gastric juice produced by the urease, which is a powerful neutralising agent. In the frequent cases of high acidity, therefore, one must assume either that the alkaline secretions are deficient or that acid secretion is increased, but this latter could only be so if the total quantity of gastric secretion were considerably larger than normal, and, on the whole, the former proposition is the more probable.

Having enumerated the defences, what of the enemy force? Pepsin, i t is thought, is the chief aggressor. " I t is generally accepted," writes FitzGerald, " that . . . pepsin catalyses the hydrolytic action of HC1 upon peptide bonds . . . pepsinogen is never secreted unless acid is also present and the acidity of a solution determines the activity of the pepsin." Pepsin will not act in a secretion of an acidity lower than pH4. Acid .and pepsin are the allies that per- ~istently assault the walls of the stomach.

Gastric Acidity. What stimulates the acid secretion of the gastric mucosa? We do

not know. Is it the needs of the pepsin ? If it is, it does not answer the question why, with a gastric ulcer the free HC1 is within the range of the normal whereas with duodenal ulcers it is usually raised and may even reach the 80's and 90's, and why in prepyloric ulcers ~here is a typical curve the first half of which is low, later rising sharply sometimes to a considerable height. These, of course, are generalisations and in individual cases the curves may be atypical; indeed, as we shall see later, acidity curve methods leave much to be desired and serve merely as an indication. For example, if a man has a high acidity shown by his test meal and has also clinical and radiological signs suggesting but not proving anything, it is fairly safe to assume that he has indeed a duodenal ulcer, which, without the evidence of the test meal, would still be a matter of doubt.

What is the value of the fractional test meal as given to-day? The fasting patient has a Ryle's tube passed down his oesophagus and is

30 IRISH JOURNAL OF MEDICAL SCIENCE

then given two cups of thin, tepid gruel to drink after a preliminary specimen of secretion has been withdrawn. For 2½ hours, thereafter, every quarter of an hour another specimen of his gastric juice is removed and the results t i trated for free HC1 and total acidity. Now, consider the method. It is well known that the mere sight or smell of a good meal will elicit gastric secretion and salivation. Par lor proved that long ago on his clogs with fistulae. Similarly a repulsive smell (e.g. of bad eggs or a decomposing body) will produce nausea, and nausea implies hyposecretion. If a person is hungry the sight of a tastefully cooked meal will, therefore, cause hyperseeretion in anticipation; but will some thin tepid gruel? Not it! One might as well offer a starving man a glass of water. On the other hand the passage of a tube down the nose or swallowed with discomfort and difficulty is likely to cause excess secretion for the patient is in an acutely nervous state--and this fact I have found experimentally to be correct, as will be explained later. So here we have two opposing factors affecting a truthful recording of internal activity. No! The only proper way of assessing gastric acidity secretion is to take a 24 hour recording two-hourly, with the patient, within the limits of hospital routine, going about his normal business, eating his norml~l food and smoking his normal quota (only at given times) so that t h e effect of the tobacco on him can also be checked. ,Charts of three such records are included here (Figs. 12-18) with the corresponding fractional test meal charts, and the variation speaks for itself. The obvious objection to this is that it entails the admission of the patient to the hospital for at least 24 hours and thus an economic and material factor becomes involved, but with that medicine ought not to be concerned. Furthermore, there is evidence to suggest that the results of test meals on the same person at different times differ considerably, and, as will be seen later, they may depend primarily on the psychological state of the man at the time of trial.

Omitting, for the moment, the treatment of hyperacidity by alkalis ~nd milk, what of the effects of diet on hyperacidity? It has been advocated that the meals of an ulcer patient should be insipid, un- attractive and merely adequate so as not to stimulate his juices. Here are no advocates of " a little of what you fancy does you good " But have you ever been very hungry? Have you ever been perforce without food for 24 hours while in perfect health, and with no immediate prospects of a meal? And then have you ever fallen asleep ? If you have, there is only one thing that will have entered your mind, you will have dreamed of a banquet with a large roast turkey as the pNce de r~sist~nce, surrounded by a mass of tasty dishes, and then y o u will have wakened. In short, a man deprived of satisfying food (and insipid food does not satisfy) will spend a great deal of his time stimu- lating his gastric juices by thoughts of " r ea l meals ". I t is noticeable how, especially during the war and even today at tea parties, in queues, in the pub or the club, conversation inevitably runs on food with reminiscences of the good old days and what they brought with them. Does, then, an "ulcer diet " afford a real reduction of the acid content of gastric juices? We shall enter more fully into this discussion hereafter.

S L E E P THERAPY IN DUODENAL ULCER 31

Achlorhydria. Sometimes the presence of free HC1 cannot be elicited from test meals.

Sometimes it can only be elicited by the injection of the substance hista- mine and sometimes it is not to be elicited under any circumstances whatever. And when this occurs in conjunction with the clinical or radiological signs of a gastric ulcer it is considered to be pathognomonie of an ulcer turned malignant. Achlorhydria can be produced by the cutting off of the blood supply to the gastric mucosa whether experi- mentally or naturally by emboli; it can also be produced temporarily by addiction to morphia and the HC1 secretion can be inhibited by the consumption of uncooked fat. I t is unlikely that there is a single ex- planation of all these phenomena, and if there is we do not know it. But the cogent question is whether the achlorhydria is due to lack of acid secretion or to excess of alkaline agents that neutralise it. And the in- teresting speculation is of the connection between achlorhydria and malignant ulcers, which also involves the problem of why there has been no known case of malignancy of a duodenal ulcer. Some people say that the duodenal ulcer cannot become malignant, but this implies an insight into the causes of such non-malignancy which we do not possess and hence it is more accurate to say that within our experience duodenal ulcers have never been known to become malignant.

Again, too, achlorhydria is not an inevitable feature of malignancy; it may exist with no gastric lesion discernible or there may be free HC1 in the presence of a cancerous ulcer. I t is another of these generalisa- tions that hold good only for a fair proportion of cases. Yet a third question can be asked on this matter. Does the achlorhydria precede the malignancy or does the malignancy sometimes produce achlorhydria? I f the former is correct then possibly the pepsin and the urease, being unopposed and, therefore, relatively excessive, cause the malignant ulcer, although we have no empirical evidence of this; and if this were so (to continue to build on hypothetical foundations) the malignant ulcer must per naturam suam differ from the ordinary gastric ulcer, and hence it is untrue to say that " gastric ulcers can become malignant." One thing at any rate is clear : that duodenal and gastric ulcers are fundamentally different and that the term " peptic ulcer " should be abolished as implying a difference between them merely of locationma view that is rapidly coming into its own.

Methods of Treatment. Ulcers may be treated either medically or surgically according to the

condition of the patient or the inclination of the attending doctor. With the surgical treatment we are not here concerned and will make no fur ther reference to it. Of the medical there are one common and two less frequently used modes of t reatment; the most usual being rest and diet with or without admission to hospital; and the less ordinary forms being by radiotherapy and by insuffiation of posterior pituitary extract, the rationale of which may become more apparent later.

X-ray irradiation of the mucosa is a new and insufficiently tried method, although not only it has had good results in some cases, but it has been possible in certain instances to follow up the post-mortem effects of patients so treated who have died from other causes, and the

32 IRISH JOURNAL OF MEDICAL SCIENCE

histology of the mucosa in cases where gastrectomies have later been performed. The main point of the method is that i t does reduce the total acidity and the total quantity of gastric juice secreted, but not permanently in all cases2

But the most important and most common form of treatment is by rest in bed and diet. Such diets may vary slightly according to whose is followed, although the Sippy diet is perhaps the best known. At all events the underlying principle is the same : to ensure constant feeds and as little overloading of the stomach as possible at the same time, while the acid is neutralised by milk and alkaline powders. During his first week in hospital the unfortunate patient is regaled with 2-4 ounces of eitrated milk every two hours, increasing in amount as the days go by and in addition the contents of " a white bottle ". For the rest he lies in bed with little to think of except his inside, or his home and work that must progress as best they can without him. Thus, although his ulcer may be the better for the neutralisation of the corrosive acid and the pain lessened by the frequent intake of fluid inhibiting peristalsis, yet the patient himself neither mentally nor physically can be said to be improved. By this method we do not treat the patient, we treat merely the ulcer.

There is a further point to be considered. Neutralisation of acid does not necessarily imply that the underlying hypersecretion is being affected in any way. Indeed, if one can suppose that the gastric mucosa has increased its acid output per necessitatem due to some undiscovered tstimulation, or, if one may speak so teleologically, for some reason of its own, then the neutralising of the HC1 as fast as it is excreted may well effect still greater activity on the part of the stomach wall in order to make up for the constant relative loss, in which case when the alkalis ,and milk drinks are at an end the free HC1 content will be even higher than before. And this is not at all unknown in the case of persons treated thus, although it is not an invariable result. Sometimes the acidity is lowered, sometimes it remains the same. But the results of test meals are so diverse that, as at present conducted, it seems that little • store should be set by them.

Brain and Mind. For centuries man has been aware of a connection between his emotions

and his stomach. He has felt physically sick with worry; certain sights --no more than sights---can actually make him vomit ; in love he loses all appetite; with acute fear diarrhoea may occur precipitously. But it is only recently that any physiological connection has been found to explain these phenomena, for the vagus nerve proved to be a red herring and vagotomy as a cure for ulcers ana hypersecretion has gone out of fashion.

Writing in 1949 Professor Fulton 6 is able to quote experiments demon- .strating the nerve paths existent between the higher parts of the brain, the hypothalamus and the alimentary tract. (Have we here, an explana- tion of the success claimed for insufflation of posterior pituitary extract?) The methods used were comparatively simple, involving the stimulation by electricity and the direct application of chemicals such as strychnine to different parts of the brain and observation of the effects of such stimulation on the body. Some years ago, Adrian of Cambridge began

FI(:. 1.

Flo 1. Ordinary tes t nleal of L. L. taken while

still an outpat ient .

Fla . 2. Twenty- four hour specimens after admis- sion. I t will be noted tha t between l l p .m. and 4 a.m. the free H C1

reaches zero.

F r ~ "2.

Fie. 3. L. L. gastric ulcer high up on lesser curvature .

FlG. 4. L . L . Long tongue of ba r ium in cavity of duodenal ulcer.

FI¢~. 5. After 2 weeks' sleep the rapy : duodenum fills well, and there is no sign of ulcer crater. Gastric ulcer still present , considerably reduced in

SiZe,

FIG. 6. After r e tu rn to work and 8 weeks af ter Fig. 5 was taken. Gastric ulcer again reduced bu t still

present. Duodenum as in Fig. 5.

L FP2AC'TIONAL TEST-MEAL D~am .~. 3.. at,

FIG. 7. T. G. tes t meal, before conserva t ive t r ea tmen t . After 6 weeks of this the acid was wi th in h igh n o r m a l l imits unlike S. H. But~ t~tis was the or~ly a,ppm*ent

i m p r o v e m e n t .

=;7

ttO{'lO

rOt'e7

*o+as

FIc~'. 8. T. G. acidity during sleep.

Fie,. 9. Ori~;inal ulcer. Fl<~, 10. After 2 weeks' sleep.

Fro. l l . After a, th i rd week's sleep.

L FK\CTtONM, TEST-M.EAL D~VB - ; I

, ~ , i ~ _ _ ± ~ . u _ I t _.

FIe. 12. S. H. f ract ional tes t meal on admission. Duodenal ulcer demons t ra ted bo th clini-

cally and radiologically.

Fro. 13. S. H. after 6 weeks of Sippy diet and alkalis. Despite the rise in acidity pa t ien t was clinically improved con-

siderably.

! B~Je " t ~

Blood i"" ~ S t . a r c h

m 0 ( - 3 6 ~ )

soC~ZT)

~0('2921

7o(-zS~l

SQ(.m2~

30(-t09~ i

Ito(.oT~)

~ONa 0 H (%Net..)

/

• , z . . , ~ ¢ ~ J

1 \

\ \ ~ K

Fir;. 14. The same dur ing sleep, taken a few nights after the test meal of Fiff. 13.

~Of'~a$1

!

~"#&S ~ . .

FIG. 15. 1). :N. acidi ty dur ing sleep as compared wi th Fig. 16. This pa t i en t had morph ine gr. :;

at l I p.m.

L FRACTIONAL TEST-MEAL, D ~ * ~, ~ • L

e,oo~ !'4 i - ' - ! S

~K)(-atm;

~ ( -3Z7

70(.aS5

60 (.'Z~9

aO(.~09

e.Ol-O?a)

J~Na OH (%~ct.,)

? 4'" I

1

I / ,

Fro. 16. ]2. N. fract ional tes t meal. This pa t ien t had a l~rge gastric ulcer, and finally h~¢l a part ial

gas t rec tomy done.

l ~1~o~

[: I - v . ,"

FIG. 17. :Nigilt acidi ty of ('. Duodenal ulcer demons t r a t ed clinically and radiologically.

Sleep wi th Soneryl.

'~,-i I I t l I I I ! | ! I I • " 1 I I I 1.1 I 1 L i d 1 I ~ - .

. , , J l| ti~ t]1 I lb4"~l:~ i l

..,..~I ~-'~I_1~I'~ I lhAl~l " "

.o,.,..i!tl t I i I ' 1/1 1 \ t 1 1 \ ! 1 -

..,,.,..~II t~ I' I ~. G 4 d I [ ~ I ~I\'l

.1,11 k-~ p,I .

Fief. 18. Twenty- four hour record of C. :Note t ha t he had no Soneryl and slept badly. His to ta l acidity was considerably raised.

Xote the s imi]ari ty in the type of curve in Figs. 14. 15 and 17. The initial rise is p robab ly due to the p u t t i n g down of the tube.

S L E E P T H E R A P Y IN D U O D E N A L U L C E R 33

this mapping out which has made so much contribution to our under- s tanding of the interaction of mind and body. The areas enumerated are approximately those of Brodmann.

Thus we read in Ful ton that Davey finds . . . that he can obtain from [stimulation of] area 8 vigorous gastric movements and increased peristalsis both in the small and large intestine, so vigorous indeed that extreme intussusception may result. Even more significant, he finds that long slowly repeated pulses cause conspicuous increase in the volume of gastric secretion and ir~ the concentration of both HC1 and pepsin. Aug- mentation in the latter was due to stomach secretion for it still occurred after the pylorus had been tied off. A n d a.f fai~ : Davey's observations have been well controlled and they indicate that both the movements of the gut and the char° acter of the gastric secretion ca~ be regulated from the cortical level.

The outstanding point of interest about this is that we have long been accustomed to associate the duodenal, i~ not the gastric, ulcer with the worrying type of personality, and with certain types of occupation, such as that of a bank manager, on whom responsibility lies heavily, or especially with economic conditions in which the family budget is reluctant to balance.

Parallel to the evidence quoted by Ful ton and complementary to it is the investigation carried out by Wolf and Wolff on their laboratory assistant, referred to throughout their book as " Tom ", who had a stoma f rom the age of 9 and whose gastric mucosa could be studied directly as well as indirectly, and on whom nearly every conceivable experiment was carried out.

Pro[ound alterations in gastric function (they write), as well as other bodily pat~rns were found t~o accompany emotional disturbances. The alterations in gastric function fell into two categories: (i) depression of acid output, motor activity and vascularity, and (ii) acceleration of ~hese functions. The former was associated with a reaction of flight or withdrawal from an emotionally charged situation. The latter accompanied a reaction of internal conflict with an unfulfilled desire for aggression and fighting back. Profound and prolonged emotional disturbances of this kind were accompanied by marked and prolonged increases in gastric mobility, secretion and vascularity with reddening and ¢ngorgement of the mucous membrane often reproducing the picture of " gastritis ". As it was possible to question Tom while observations were being made, it was fur ther elicited that hyperact ivi ty of the stomach was associated with hear tburn and epigastrie pain of a gnawing kind present when the stomach was empty, and which was relieved by food, milk and alkalis, a n d that hypoact ivi ty was represented by feelings of fullness in the epigastrium and nausea with diarrhoea and hypogastrie cramps. Both descriptions are familiar.

But now perhaps one or two facts, which have hitherto hung loosely about, may be knitted together. F rom observation of Tom's mucosa it was evident that hyperact ivi ty meant increased vascularity and hence, conversely, anaemia spells achlorhydria if the anaemia is of sufficient degree. But for the oxyntic cells to be inactivated the anmmia must be fair ly general so as to involve the comparatively large area of the fundus ; but what of a narrowly circumscribed local lesion? FitzGerald and Murphy suggest that gastric ulcers first begin by failure of the produc- tion of urease through a vascular spasm or a block in the blood stream by a local embolus. I f this lesion should occur while the stomach as a whole was in a hyperactive state due to cortical stimulation (known popularly as worry) then the deficiency of urease and mucus at a single point would offer a defeneeless area to the products of the fundus.

34 IRISH JOURNAL OF MEDICAL SCIENCE

It is of interest here to note that Hippocrates, in attempting to heal his ulcer case, and finding that purgatives and emetics did no good, finally bled the man almost white and procured thereby relief from his symptoms; but unforunately not for long, for the man died. However, he had chanced on the right principle, viz., that of obtaining avascularity, even if he used the wrong method to secure results.

Wolf and Wolff found that mere scratching of the mucosa so as to cause bleeding produced no ~edema or inflammation, nor was Tom aware of any pain or discomfort. Mucosa collected over the lesion and in a short time the place was healed. Similarly if N/1 HC1 was allowed to drip on to the mucous membrane the only result was an increased output of the mucus, forming flakes that were insoluble in the acid. On the other hand, if the mucus was not allowed to settle, but was scraped away the HC1 made the mucosa red and cedematous and a lesion then made ted to bleeding, and bleeding in its turn led to even further acid secretion. This, they suggest, may explain the hyperacidity of the peptic ulcer patient, being the creation of a vicious circle. But if that were so one would imagine that there would always be a strongly positive blood reaction in gastric juice drawn off where there is hyperacidity, yet this is not borne out by the results of test meals.

Two other experiments are of some clinical interest with a view to visualising what is happening when a patient speaks of his symptoms, namely, those of the effects of pressure and the effects of distension. Light pressure Tom apparently could feel as he felt light pressure any- where, but deep pressure was represented as a pain of a steady deep, dull, gnawing character in the region of the stimulus. When distention was produced by the insertion of a rubber balloon, then blown up and carefully controlled, pain was felt through the whole epigastrium and sometimes in the sides and back as well; this was of a dull aching type accompanied by nausea and described as " a sickening type of pain ". Patients use identical terms to describe their pain to which can thus be allotted at least the mechanical cause.

One point, however, these two workers make again and again through- out their book, namely, that the activity of the gastric mucosa depends on the emotional state of the patient; they observed that whenever Tom was resentful or angry or worrried his stomach wall was engorged, highly vascular and hyperactive. Stimulation of area 8 of the cortex produces gastric hypersecretion.

Steep Therapy. Starting from this premise of Fulton's it is not a long step to infer

that by cutting off as far as possible all cortical stimulation of the gastric wall, i.e., preventing the patient from thinking or worrying, one would be providing the best possible conditions for the healing of an ulcer. And such was the hypothesis on which further investigation was based.

First it was necessary to discover whether there was an alteration in the gastric secretion during profound sleep. According to Wolf and Wolff if Tom went to sleep with a quiet mind his mucosa remained pale and inactive, but if in a disturbed state sleep did not alter its engorged and reddened appearance. But all sleep is not of the same quality, and there are times when we wake "as a giant refreshed ", but at others we

S L E E P T H E R A P Y IN D U O D E N A L U L C E R 35

spend a night of tossing and turn ing and dreaming and waken no less tired than when we went to sleep. Hence the sleep to be aimed at was the deep and dreamless type, that in which 8 waves supercede the a waves on an electroencephalographie recording.

Hence the nocturnal secretion was tested of thirteen patients who slept soundly on 2 Soneryl tablets with a Ryle 's tube passed down at 9 p.m. and through which 2-hourly specimens of gastric juice were drawn off for the most par t without the patient waking. Each patient had previously had a routine test meal which had shown a high or comparatively high acidity. Of these 13, 9 showed a marked reduction in the HC1 and of the 9, 6 went down to zero between the hours of 1 a.m. and 5 a.m. In any case when a patient reported having had a bad night for one reason or another the acid did not go down, indeed it tended to be higher than dur ing the test meal. One patient who had had a reduced acidity during sleep with Soneryl subsequently had a 24 hour test done and insisted this time that he could sleep well without tablets. This t ime his acid was high and he confessed in the morning that he had slept badly, having been awake until 1 a.m. and again from 3 a.m. to 4 a.m. (See Figs. 7-18.)

Now Voegtler, s of Seattle, tested the nocturnal acidities in 13 normal and 53 duodenal ulcer cases and reported that there was no significant decrease in acid secretion dur ing the night. F rom his account, however, there is nothing to show that he took any measures to ensure a good n ight ' s rest, but he tested with (i) gr. 1/100 atropine, (ii) 2-hourly milk and alkalis, (iii) lavage and a sodium solution given at 9 p.m. without finding any decrease, while (iv) with Sippy powder it was slightly lowered at 1 a.m. and (v) with oleic acid there was some small inhibitio~ 5 hours later. Thus, from the evidence presented, the results axe no t ¢ompaxable.

As our investigations were carried out in a general hospital where ulcer patients formed but a small percentage of the whole, it was decided that the results, few though they were, were sufficient to jus t i fy an ex- periment upon a patient suffering from a double ulcer whose clinical condition was extremely poor and who also was regarded as unsuitable for operation. The patient himself was aware that it was experimental t reatment as f a r as ulcers were coneerned, but was more than ready to t r y anything that might relieve the pain.

OASE HISTORY 1. L.L. P.O. engineer. Age 55, married, 13 children. In August, 1949, pain began to be felt in patient's left side and worked roun~f

to his back. A slight improvement resulted after a diet and alkalis had been given him by his doctor, but in October there was an exacerbation of th~ symptoms whet. the pain .became acute and centred in the lower dorsal and lumbar region of the back. Port's caries was at first suspected but the ~-ray proved negative. A chest x-ray showed a healed focus in the left apex. Finally, z-ray of the G.I.T. showed a large duodenal and larger gastric ulcer (Figs. 3, 4), the latter on the upper part of the lesser curvature. While waiting for a bed he was given strict dieting rules to which he adhered closely, but his clinical condition was obviously deteriorating, and by the time he was admitted to hospital in January of this year, his skin was dry and sallow, his eyes were sunken and with black rings round them and he was permanently stooped with the pain, which now never left his back and from which he only had slight relief for a short time after a light meal. But food now nauseated him and he had vomited occasionally. His acidity was high, but a 24-hour test showed a .zero reduction, during sleep on Soneryl. (Figs. 1 and 2.)

The sleep therapy was naturally modified by the limitations of non-specialised nursing and general hospital routine; however, during the 2 weeks of th~

36 IRISH JOURNAL OF MEDICAL SCIENCE

t r e a t m e n t , L.L. had about 20 hours ' sleep out of the 24. He was pu t in to a room by himself and a fluids requi rements char t was drawn up to ensure sufficient in take. Casinal and Mul t iv i te tablets were added to the diet , which was in o ther respects as near ly normal as possible, there being no special pro- vision for alkalis unless reques ted by the p a t i e n t a t any t ime. Emphas is was, however, laid upon a pro te in r a the r t h a n a carbohydrate diet , as the au thor is less convinced t h a t bread is the staff of life t h a n t h a t i t is " t h a t peri lous stuff which weighs upon the hea r t "

Diet Chart. 6.30 a.m. P o r r i dge and milk. 2 cups of tea. Egg flip. Bread and bu t te r .

7 a.m. Soneryl tabs ii. 9.30 a .m. Glass of milk and Casinal.

9.45 a.m. Soneryl tabs ii. 12.30 p.m. Cup of soup (non-greasy)--glass of mi lk- -g lass of water. Creamed

chicken, fish, rabb i t or mince. Mashed potatoes. Milk pudd ing or jelly. 2 cups of tea.

1 p .m. Soneryl tabs ii. 3.~10 p .m. 2 cups of tea. Sponge cake or biscuits.

4 p.m. ,Soneryl tabs ii. 6.30 p .m. E g g flips or l ight ly boiled egg. Glass of milk and Casinal.

Biscuits and cheese or mince an<l slice e l bread, 2 cups of tea. 7 p.m. Soneryl tabs ii.

10.30 p.m. {2up of cocoa. 2 cups of tea. .Sponge cake or biscuits. 11 p.m. Soneryl tabs ii.

I n cons t ruc t ing the die t the emphasis was laid on wha t the p a t i en t liked if th i s were possible. Tea was given weak and wi th sugar or glucose and the fluid in take had less regard for the ulcer t han for the need to make up loss by excre t ion dur ing sleep. The pa t i en t was allowed visi tors dur ing his lunch hour.

t in the second day he vomited, and on the t h i r d day the d r ink a t 9.30 a.m. was added, as he found t h a t pa in awoke him from too long a fas t ing period. F rom the four th day onward he never looked back. I n a week he had so obviously pu t on weight t h a t his wife commented on i t ; his skin became shinier ~nd he admi t t ed to developing an appe t i t e such as he had no t known in

months. Moreover, the pa in and the t enderness s teadi ly decreased unt i l , at t h e end of 2 weeks, the only pa in he complained of a t all was due to wind.

X-ray examina t ion confirmed the clinical f indings as far as the duodenal ulcer wa~ concerned. (Figs 5-6.) The duodenal bulb filled completely and there was no sign of the long tongue of ba r ium which had marked the ulcer in t he previous film. Bu t the gas t r ic ulcer, though much diminished in size, was still apparen t , so, to t ry and dispose of i t as well, the p a t i e n t was sent up to the pr iva te nurs ing home of t he v is i t ing psychia t r i s t to the hospi ta l wlm had facilit ies for more per fec t s leeping condit ions. Af te r another week the ~-ray showed a f u r t h e r d iminished bu t still obvious gas t r ic ulcer and an un impa i red duodenum. The p a t i e n t was then d ischarged, as he was wi thout pa in and in his own words " fel t g r a n d " , and weighed a s tone more t h a n on admission. Af ter 10 days' convalescence he went back to work, 1 month f rom the da te th a t he entered hospital , to find himself a source of in te res t as " the s leeping man "

At the end of ano ther month fu r t he r ~-ray examina t ion showed the duodenum still healed and the gast r ic ulcer again decreased bu t just visible. He was put on no special diet , bu t was warned to avoid foods likely to damage the mueosa, such as seed-jams, raw vegetables and f ru i t , and to cont inue t ak ing Casinal.

Before proceeding to the second case there are a few points to be noted here. First, the ulcers were of short duration, as far as can be determined; secondly, the acid went down to zero during sleep; thirdly, the patient was intelligent and co-operative though somewhat neurotic. These three facts made him an excellent subject for an initial experi- ment. But the chief point of interest is that the gastric ulcer did not respond with the same rapidity as did the duodenal ; nor is it healed yet (August, 1950). Although there is no sign of a recurrence of the duodenal, yet normally, on the Sippy diet, the gastric ulcer responds well whereas the duodenal is seldom healed within the statutory six weeks and indeed may persist for years despite treatment. This again suggests that ulcers in the two sites are fundamentally different. Finally, mention must be made of the fact that the patient was allowed to smoke

SLEEP THERAPY IN DUODENAL ULCER 37

cigarettes af ter any meal if he so desired before going to sleep again. _Pax menlis, corporis pax, as one might say! During 24-hour tests of secretion cigarette smoking at a given t ime was seen in all three cases to make no difference to the acid level. This was confirmed also in Wolf and Wolff's experiments, in which no change in the mucosa could be observed so long as the smoke was enjoyed and not forced upon Tom.

CASE HISTORY II . T.G. F a r m labourer, age 34. unmarr ied . For 2 years pas t the pa t i en t had a feeling which he described as one of

soreness in the abdomen, especially in the midl ine above the umbilicus, which region was very t ende r on palpat ion. He also complained of an excessive amount of flatulence. He had been p u t on a milk die t by his doctor and given " a white bott le ' which rel ieved him only sl ightly and he had pos tponed coming in to hospi ta l aga ins t t he advice of his doctor. However, he a r r ived eventual ly early in February , as his pa in was becoming worse and in t e r fe r ing wi th his work. An z- ray film showed a duodenum deformed and t ender wi th an ulcer c ra te r visible, t t i s acid, as shown by a tes t meal, was high. H e was p u t on the Sippy die t of. 2 hourly .milk feeds wi th alkaline powder for 6 weeks gradual ly up to the l ight diet normal to th is k ind of t r e a t m e n t . His pa in , unfor tunate ly , did not improve and the tenderness was still .marked and a f u r t he r z- ray showed the duodenum still deformed and ulcer c ra te r present . The only improvement was a decrease in the acid level to t h a t of a high normal.

This p a t i e n t was not satisfied wi th his progress and, hav ing seen L.L. , who had visi ted the ward while r e t u r n i n g for a check z-ray, demanded t h a t he, too, should be pu t to sleep and have his ulcer cured. As the conservat ive t r e a t m e n t had failed, i t was decided to give the more unor thodox method a t r ia l , so a t e s t of his noc turna l juice was t aken dur ing sleep on Soneryl and the results showed almost complete achlorhydria , unlike the curve of his t e s t meal. (Figs. 7 and 8.) This, combined with his complete fa i th in the therapy, weighed aga ins t the 2 years ' du ra t ion of the ulcer and he was, therefore , pu t into a room by himself and given the same die t as L.L. , except t h a t ,milk and water was subs t i tu ted for t ea a t his own request .

Like L.L. , he vomited on the second and again on the t h i r d day, but there - a f te r made considerable improvement in genera l appearance and in reduct ion of the pa in and tenderness . As the end of 2 weeks he was again z-rayed~ the duodenum being slow in filling and showing a small fleck of bar ium cons tan t in each film, proving t h a t the ulcer was not yet fully healed~ a l though there seamed to be a marked decrease in its size. He was, therefore , pu t to sleep again for another week. The final z- ray, as can be seen, shows no fleck of bar ium com- parable with t h a t in the previous p ic ture , though there is still some spasm of the pylorus and the radiologis t ' s r epor t was t h a t no ulcer was visible. (Figs. 9-11.) The pa t i en t ' s clinical condi t ion also suggests t h a t a cure has been effected. He, too, s ta ted t h a t he " fel t g rand " , and there is only a s l ight general ised soreness and no tenderness even on deep palpat ion.

Discussion. Two instances are na tura l ly insufficient to establish a proof of any

theory but, coupled with the results of nocturnal secretion tests and cold logic, they are, we think, adequate grounds for offering them as a basis for fu r the r investigation into a method of t reatment which may reduce the length of t ime ulcer patients have to endure the all too well- known effects of their condition.

I t was fortunate, too, that one of the cases had both a duodenal and a gastric ulcer for, omnibus paribus, it is possible to infer that the gastric ulcer is f a r more resistant to this kind of t reatment than to the common method of dieting. Had the essay been made on two different patients, one suffering from a duodenal and one from a gastric ulcer, a dozen reasons might have been pu t forward as to why the one reacted and the other did not or did so only in a lesser degree. But at least one point can again be emphasised: that the distinction between duodenal and gastric ulcers is becoming more and more marked; that, as was said above, it seems likely that they are fundamental ly different lesions.

These investigations do not, of course, throw any light on the vexed

38 I R I S H JOURNAL OF M E D I C A L S C I E N C E

question of the cause of ulcers, but they do substantiate the hypothesis that the brain assists in preventing healing once the ulcer has appeared. Again, it throws no light on the causes of a raised acidity nor does i t help to decide whether the rise in acidi ty precedes, is concomitant with, or succeeds the ulcer. But they are consistent with the experimental evidence offered by Ful ton on the functions of the frontal lobes. One could say at the outset : " I f Fu l ton is r ight then such and such an event will occur ." And so far, in the case of the duodenum, the expected result did occur.

We should like to suggest tha t confirmation be sought first among patients whose ulcers are of recent origin, in which fibrosis is less likely to have taken place, and that these ulcers shall be duodenal and that the pat ient ' s sleep acidity is zero or near ly zero. And here i t might be well to add that Wolf and Wolff, in a pr ivate communication, reiterate that in their opinion it is essential tha t the pat ient goes to sleep in a state of reassurance ; and whether Soneryl or intravenous Nembutal or any other non-gastric st imulating drug can overcome the emotional state is still a mat te r for experiment.

F o r obvious reasons no claim can yet be made with regard to the durabi l i ty of the cure, but there seems no reason to suppose that it will be less lasting than those produced by the ordinary conservative treat- ment. Healing is healing, by whatever method it is attained. Moreover, its only claim to bet ter ing the ordinary methods is that it appears to produce results in a shorter time, which is worthy of consideration not only f rom the pat ient ' s point of view, important though that is, but also f rom that of the hospital whose beds are emptied more quickly in eases sufficiently serious to merit admission. Finally, it is worth asking : what would be the effects of sleep the rapy on early ulcerative colitis?

Sedation, which has been t r ied with a degree of success over a period of time seems to the author to be but a half measure and a too timorous approach. And Russian experiments 9 in sleep therapy, in so f a r as they have been reported, give insufficient detail to enable one to say how f a r their unsuccessful results were comparable with these. Sleep, deep and dreamless, will, we are convinced, give any physical lesion the best means of healing rapidly, provided a watchful eye be kept on the possibility of chest complications of which we have seen no sign in our two patients.

The suggested remedy, therefore, fo r duodenal ulcers is " b u t a sleep and a forget t ing."

1 should like to express my appreciation to Professor V. M. 8ynge for granting me facilities for testing my theories, to Dr. Eustace for advising as to the method of narcotherapy and especially to Dr. R. Wilson for encouraging my theorising in the midst of scepticism.

Bibliography. 1--Hippocrates. (Edn. Foesius, 1595). Epidemics V, Episode 6. 'J. Major, R. (1949). Classical Descriptions ot Disease. BlackweU. ~. H®r~hell, t~. (1910). Jo. C'li~. Me~., XXXVI, 18. d. Fitzgerald, O., and Murphy, P. (1950). Irish Jo. Med. ~c{., VI, 291, 97. 5. Me(Jeorge, M. (1950). Q. Jo. l~ed., Vol. XIX. a~ Fulton, J. (1949). Funetionat Loca~isation in the ~ronta~ Lobes and

~ ¢bCqum. Oxford Univ. Press. . Wolf, H., and Wolff, S. (1947). Human Gastric Function. Oxford.

8. Veegtler, V. (1946). Gastroenterology, VII, 625. M. S~vesin and Colsocopor (1950). l~cerpta Medica., Sect. VI, Vol. IV,

No. 7, p. 46~.